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Tinkering with Roundworm Proteins Offers Hope for Anti-aging Drugs
- The somatic nuclear protein kinase VRK-1 increases the worm’s lifespan through AMPK activation, and this mechanism can be applied to promoting human longevity, the study reveals. - KAIST researchers have been able to dial up and down creatures’ lifespans by altering the activity of proteins found in roundworm cells that tell them to convert sugar into energy when their cellular energy is running low. Humans also have these proteins, offering up the intriguing possibilities for developing longevity-promoting drugs. These new findings were published on July 1 in Science Advances. The roundworm Caenorhabditis elegans (C. elegans), a millimeter-long nematode commonly used in lab testing, enjoyed a boost in its lifespan when researchers tinkered with a couple of proteins involved in monitoring the energy use by its cells. The proteins VRK-1 and AMPK work in tandem in roundworm cells, with the former telling the latter to get to work by sticking a phosphate molecule, composed of one phosphorus and four oxygen atoms, on it. In turn, AMPK’s role is to monitor energy levels in cells, when cellular energy is running low. In essence, VRK-1 regulates AMPK, and AMPK regulates the cellular energy status. Using a range of different biological research tools, including introducing foreign genes into the worm, a group of researchers led by Professor Seung-Jae V. Lee from the Department of Biological Sciences at KAIST were able to dial up and down the activity of the gene that tells cells to produce the VRK-1 protein. This gene has remained pretty much unchanged throughout evolution. Most complex organisms have this same gene, including humans. Lead author of the study Sangsoon Park and his colleagues confirmed that the overexpression, or increased production, of the VRK-1 protein boosted the lifespan of the C. elegans, which normally lives just two to three weeks, and the inhibition of VRK-1 production reduced its lifespan. The research team found that the activity of the VRK-1-to-AMPK cellular-energy monitoring process is increased in low cellular energy status by reduced mitochondrial respiration, the set of metabolic chemical reactions that make use of the oxygen the worm breathes to convert macronutrients from food into the energy “currency” that cells spend to do everything they need to do. It is already known that mitochondria, the energy-producing engine rooms in cells, play a crucial role in aging, and declines in the functioning of mitochondria are associated with age-related diseases. At the same time, the mild inhibition of mitochondrial respiration has been shown to promote longevity in a range of species, including flies and mammals. When the research team performed similar tinkering with cultured human cells, they found they could also replicate this ramping up and down of the VRK-1-to-AMPK process that occurs in roundworms. “This raises the intriguing possibility that VRK-1 also functions as a factor in governing human longevity, and so perhaps we can start developing longevity-promoting drugs that alter the activity of VRK-1,” explained Professor Lee. At the very least, the research points us in an interesting direction for investigating new therapeutic strategies to combat metabolic disorders by targeting the modulation of VRK-1. Metabolic disorders involve the disruption of chemical reactions in the body, including diseases of the mitochondria. But before metabolic disorder therapeutics or longevity drugs can be contemplated by scientists, further research still needs to be carried out to better understand how VRK-1 works to activate AMPK, as well as figure out the precise mechanics of how AMPK controls cellular energy. This work was supported by the National Research Foundation (NRF), and the Ministry of Science and ICT (MSIT) of Korea. Image credit: Seung-Jae V. LEE, KAIST. Image usage restrictions: News organizations may use or redistribute this image, with proper attribution, as part of news coverage of this paper only. Publication: Park, S., et al. (2020) ‘VRK-1 extends life span by activation of AMPK via phosphorylation’. Science Advances, Volume 6. No. 27, eaaw7824. Available online at https://doi.org/10.1126/sciadv.aaw7824 Profile: Seung-Jae V. Lee, Ph.D. Professor email@example.com https://sites.google.com/view/mgakaist Molecular Genetics of Aging Laboratory Department of Biological Sciences Korea Advanced Institute of Science and Technology (KAIST) https://www.kaist.ac.krDaejeon 34141, Korea (END)
A Study Finds Neuropeptide Somatostatin Enhances Visual Processing
Researchers have confirmed that neuropeptide somatostatin can improve cognitive function in the brain. A research group of Professor Seung-Hee Lee from the Department of Biological Sciences at KAIST found that the application of neuropeptide somatostatin improves visual processing and cognitive behaviors by reducing excitatory inputs to parvalbumin-positive interneurons in the cortex. This study, reported at Science Advances on April 22nd (EST), sheds a new light on the therapeutics of neurodegenerative diseases. According to a recent study in Korea, one in ten seniors over 65 is experiencing dementia-related symptoms in their daily lives such like memory loss, cognitive decline, and motion function disorders. Professor Lee believes that somatostatin treatment can be directly applied to the recovery of cognitive functions in Alzheimer’s disease patients. Professor Lee started this study noting the fact that the level of somatostatin expression was dramatically decreased in the cerebral cortex and cerebrospinal fluid of Alzheimer’s disease patients Somatostatin-expressing neurons in the cortex are known to exert the dendritic inhibition of pyramidal neurons via GABAergic transmission. Previous studies focused on their inhibitory effects on cortical circuits, but somatostatin-expressing neurons can co-release somatostatin upon activation. Despite the abundant expression of somatostatin and its receptors in the cerebral cortex, it was not known if somatostatin could modulate cognitive processing in the cortex. The research team demonstrated that the somatostatin treatment into the cerebral cortex could enhance visual processing and cognitive behaviors in mice. The research team combined behaviors, in vivo and in vitro electrophysiology, and electron microscopy techniques to reveal how the activation of somatostatin receptors in vivo enhanced the ability of visual recognition in animals. Interestingly, somatostatin release can reduce excitatory synaptic transmission to another subtype of GABAergic interneurons, parvalbumin (PV)-expressing neurons. As somatostatin is a stable and safe neuropeptide expressed naturally in the mammalian brain, it was safe to be injected into the cortex and cerebrospinal fluid, showing a potential application to drug development for curing cognitive disorders in humans. Professor Lee said, “Our research confirmed the key role of the neuropeptide SST in modulating cortical function and enhancing cognitive ability in the mammalian brain. I hope new drugs can be developed based on the function of somatostatin to treat cognitive disabilities in many patients suffering from neurological disorders.” This study was supported by the National Research Foundation of Korea. Publication: Song, Y. H et al. (2020) ‘Somatostatin enhances visual processing and perception by suppressing excitatory inputs to parvalbumin-positive interneurons in V1’, Science Advances, 6(17). Available online at https://doi.org/10.1126/sciadv.aaz0517 Profile: Seung-Hee Lee Associate Professor firstname.lastname@example.org https://sites.google.com/site/leelab2013/ Sensory Processing Lab (SPL) Department of Biological Sciences (BIO) Korea Advanced Institute of Science and Technology (KAIST) Profile: You-Hyang Song Researcher (Ph.D.) email@example.com SPL, KAIST BIO Profile: Yang-Sun Hwang Researcher (M.S.) firstname.lastname@example.org SPL, KAIST BIO (END)
Scientists Discover the Mechanism of DNA High-Order Structure Formation
(Molecular structures of Abo1 in different energy states (left), Demonstration of an Abo1-assisted histone loading onto DNA by the DNA curtain assay. ) The genetic material of our cells—DNA—exists in a high-order structure called “chromatin”. Chromatin consists of DNA wrapped around histone proteins and efficiently packs DNA into a small volume. Moreover, using a spool and thread analogy, chromatin allows DNA to be locally wound or unwound, thus enabling genes to be enclosed or exposed. The misregulation of chromatin structures results in aberrant gene expression and can ultimately lead to developmental disorders or cancers. Despite the importance of DNA high-order structures, the complexity of the underlying machinery has circumvented molecular dissection. For the first time, molecular biologists have uncovered how one particular mechanism uses energy to ensure proper histone placement onto DNA to form chromatin. They published their results on Dec. 17 in Nature Communications. The study focused on proteins called histone chaperones. Histone chaperones are responsible for adding and removing specific histones at specific times during the DNA packaging process. The wrong histone at the wrong time and place could result in the misregulation of gene expression or aberrant DNA replication. Thus, histone chaperones are key players in the assembly and disassembly of chromatin. “In order to carefully control the assembly and disassembly of chromatin units, histone chaperones act as molecular escorts that prevent histone aggregation and undesired interactions,” said Professor Ji-Joon Song in the Department of Biological Sciences at KAIST. “We set out to understand how a unique histone chaperone uses chemical energy to assemble or disassemble chromatin.” Song and his team looked to Abo1, the only known histone chaperone that utilizes cellular energy (ATP). While Abo1 is found in yeast, it has an analogous partner in other organisms, including humans, called ATAD2. Both use ATP, which is produced through a cellular process where enzymes break down a molecule’s phosphate bond. ATP energy is typically used to power other cellular processes, but it is a rare partner for histone chaperones. “This was an interesting problem in the field because all other histone chaperones studied to date do not use ATP,” Song said. By imaging Abo1 with a single-molecule fluorescence imaging technique known as the DNA curtain assay, the researchers could examine the protein interactions at the single-molecule level. The technique allows scientists to arrange the DNA molecules and proteins on a single layer of a microfluidic chamber and examine the layer with fluorescence microscopy. The researchers found through real-time observation that Abo1 is ring-shaped and changes its structure to accommodate a specific histone and deposit it on DNA. Moreover, they found that the accommodating structural changes are powered by ADP. “We discovered a mechanism by which Abo1 accommodates histone substrates, ultimately allowing it to function as a unique energy-dependent histone chaperone,” Song said. “We also found that despite looking like a protein disassembly machine, Abo1 actually loads histone substrates onto DNA to facilitate chromatin assembly.” The researchers plan to continue exploring how energy-dependent histone chaperones bind and release histones, with the ultimate goal of developing therapeutics that can target cancer-causing misbehavior by Abo1’s analogous human counterpart, ATAD2. Profile -Professor Ji-Joon Song ( www.song-kaist.org) Associate Professor Department of Biological Sciences Email:email@example.com KI for the BioCentury (https://kis.kaist.ac.kr/index.php?mid=KIB_O) KAIST -Dr. Carol Cho Department of Biological Sciences The Research Center for Natural Sciences KI for the BioCentury (https://kis.kaist.ac.kr/index.php?mid=KIB_O) KAIST
A Single, Master Switch for Sugar Levels?
When a fly eats sugar, a single brain cell sends simultaneous messages to stimulate one hormone and inhibit another to control glucose levels in the body. Further research into this control system with remarkable precision could shed light on the neural mechanisms of diabetes and obesity in humans . A single neuron appears to monitor and control sugar levels in the fly body, according to research published this week in Nature. This new insight into the mechanisms in the fly brain that maintain a balance of two key hormones controlling glucose levels, insulin and glucagon, can provide a framework for understanding diabetes and obesity in humans. Neurons that sense and respond to glucose were identified more than 50 years ago, but what they do in our body has remained unclear. Researchers at the Korea Advanced Institute of Science and Technology (KAIST) and New York University School of Medicine have now found a single “glucose-sensing neuron” that appears to be the master controller in Drosophila, the vinegar fly, for maintaining an ideal glucose balance, called homeostasis. Professor Greg Seong-Bae Suh, Dr. Yangkyun Oh and colleagues identified a key neuron that is excited by glucose, which they called CN neuron. This CN neuron has a unique shape – it has an axon (which is used to transmit information to downstream cells) that is bifurcated. One branch projects to insulin-producing cells, and sends a signal triggering the secretion of the insulin equivalent in flies. The other branch projects to glucagon-producing cells and sends a signal inhibiting the secretion of the glucagon equivalent. When flies consume food, the levels of glucose in their body increase; this excites the CN neuron, which fires the simultaneous signals to stimulate insulin and inhibit glucagon secretion, thereby maintaining the appropriate balance between the hormones and sugar in the blood. The researchers were able to see this happening in the brain in real time by using a combination of cutting-edge fluorescent calcium imaging technology, as well as measuring hormone and sugar levels and applying highly sophisticated molecular genetic techniques. When flies were not fed, however, the researchers observed a reduction in the activity of CN neuron, a reduction in insulin secretion and an increase in glucagon secretion. These findings indicate that these key hormones are under the direct control of the glucose-sensing neuron. Furthermore, when they silenced the CN neuron rendering dysfunctional CN neuron in flies, these animals experienced an imbalance, resulting in hyperglycemia – high levels of sugars in the blood, similar to what is observed in diabetes in humans. This further suggests that the CN neuron is critical to maintaining glucose homeostasis in animals. While further research is required to investigate this process in humans, Suh notes this is a significant step forward in the fields of both neurobiology and endocrinology. “This work lays the foundation for translational research to better understand how this delicate regulatory process is affected by diabetes, obesity, excessive nutrition and diets high in sugar,” Suh said. Profile: Greg Seong-Bae Suh firstname.lastname@example.org Professor Department of Biological Sciences KAIST (Figure: A single glucose-excited CN neuron extends bifurcated axonal branches, one of which innervates insulin producing cells and stimulates their activity an the other axonal branch projects to glucagon producing cells and inhibits their activity.)
Professor Ki-Jun Yoon selected as the 2019 SUHF Young Investigator
< Professor Ki-Jun Yoon > Professor Ki-Jun Yoon from the Department of Biological Sciences was named one of four recipients of the 2019 Suh Kyung-Bae Science Foundation (SUHF) Young Investigator Awards. The SUHF is a non-profit organization established in 2016 and funded by a personal donation of 300 billion KRW in shares from Chairman and CEO Kyung-Bae Suh of the Amorepacific Group. The primary purpose of the foundation is to serve as a platform to nurture and provide comprehensive long-term support for creative and passionate young Korean scientists committed to pursuing research in the field of life sciences. The SUHF selects three to five scientists through an open recruiting process every year, and grants each scientist a maximum of 2.5 billion KRW over a period of up to five years. Since January this year, the foundation received 83 research proposals from scientists across the nation, especially from those who had less than five years of experience as professors, and selected the four recipients, including Professor Yoon. Professor Yoon was recognized for his contributions to the advancement of research on how post-transcriptional mechanisms may modulate stem cell properties. His research project involves deciphering the molecular mechanisms controlling RNA metabolism in neural stem cells during normal development, and how alterations in RNA regulatory programs lead to human brain disorders. < (From left) Professor Joo-Hong Park, Professor Yuree Lee, Chairman and CEO Kyung-Bae Suh, Professor Eunjung Lee, Professor Ki-Jun Yoon, ⓒ Amorepacific Group > The other awards were given to Professor Joo-Hong Park and Professor Yuree Lee of Seoul National University, and Professor Eunjung Lee of Boston Children's Hospital and Harvard Medical School. The awards ceremony was held on September 18 at the Amorepacific Headquarters in Seoul. With these four new awardees, a total of 14 scientists have been named as SUHF Young Investigators to date. (END)
Two More Cross-generation Collaborative Labs Open
< President Sung-Chul Shin (sixth from the left) and Professor Sun Chang Kim (seventh from the left) at the signboard ceremony of KAIST BioDesigneering Laboratory > KAIST opened two more cross-generation collaborative labs last month. KAIST BioDesigneering Laboratory headed by Professor Sun Chang Kim from the Department of Biological Sciences and Nanophotonics Laboratory led by Professor Yong-Hee Lee from the Department of Physics have been selected to receive 500 million KRW funding for five years. A four-member selection committee including the former President of ETH Zürich Professor Emeritus Ralph Eichler and Professor Kwang-Soo Kim of Harvard Medical School conducted a three-month review and evaluation for this selection to be made. With these two new labs onboard, a total of six cross-generation collaborative labs will be operated on campus. The operation of cross-generation collaborative labs has been in trial since March last year, as one of the KAIST’s Vision 2031 research innovation initiatives. This novel approach is to pair up senior and junior faculty members for sustaining research and academic achievements even after the senior researcher retires, so that the spectrum of knowledge and research competitiveness can be extended to future generations. The selected labs will be funded for five years, and the funding will be extended if necessary. KAIST will continue to select new labs every year. One of this year’s selectees Professor Sun Chang Kim will be teamed up with Professor Byung-Kwan Cho from the same department and Professor Jung Kyoon Choi from the Department of Bio and Brain Engineering to collaborate in the fields of synthetic biology, systems biology, and genetic engineering. This group mainly aims at designing and synthesizing optimal genomes that can efficiently manufacture protein drug and biomedical active materials. They will also strive to secure large amounts of high-functioning natural active substances, new adhesive antibacterial peptides, and eco-friendly ecological restoration materials. It is expected that collaboration between these three multigenerational professors will help innovate their bio-convergence technology and further strengthen their international competitiveness in the global bio-market. Another world-renowned scholar Professor Yong-Hee Lee of photonic crystal laser study will be joined by Professor Minkyo Seo from the same department and Professor Hansuek Lee from the Graduate School of Nanoscience and Technology. They will explore the extreme limits of light-material interaction based on optical micro/nano resonators, with the goal of developing future nonlinear optoelectronic and quantum optical devices. The knowledge and technology newly gained from the research are expected to provide an important platform for a diverse range of fields from quantum communications to biophysics. (END)
Professor Sang Gyu Kim Receives Yeochon Award for Ecology
Professor Sang-Gyu Kim from the Department of Biological Sciences was selected as the winner of the 12th Yeochon Award for Ecology presented by the Yeochon Association for Ecological Research. The award was conferred on August 13 in Jeju at the annual conference co-hosted by the Ecological Society of Korea and the Yeochon Association for Ecological Research. Professor Kim received 10 million KRW in prize money. Professor Kim was recognized for his achievements and contributions in studying herbivorous insects ‘rice weevils’ and their host plant ‘wild tobacco’, especially for having explored the known facts in traditional ecology at the molecular level. His findings are presented in his paper titled ‘Trichobaris weevils distinguish amongst toxic host plants by sensing volatiles that do not affect larval performance’ published in Molecular Ecology in July 2016. Furthermore, Professor Kim’s research team is continuing their work to identify the ecological functions of plant metabolites as well as interactions between flowers and insect vectors at the molecular level. In doing so, the team edits genes in various plant species using the latest gene editing technology. The Yeochon Award for Ecology was first established in 2005 with funds donated by a senior ecologist, the late Honorary Professor Joon-Ho Kim of Seoul National University. The award is named after the professor’s pen name “Yeochon” and is intended to encourage promising next-generation ecologists to produce outstanding research achievements in the field of basic ecology. Professor Kim said, “I will take this award as encouragement to continue taking challenging risks to observe ecological phenomenon from a new perspective. I will continue my research with my students with joy and enthusiasm.”
Professor Jin Woo Kim Wins the 14th Macrogen Scientist Award
Professor Jin Woo Kim of the Department of Biological Sciences at KAIST received the 14th Macrogen Scientist Award at the 2017 KSMCB International Conference held in COEX on September 12, 2017. The award is given by the Korean Society for Molecular and Cellular Biology (KSMCB) and sponsored by Macrogen, a service provider of genome research. The award was established in 2004 to recognize biological scientists who have accomplished excellent performance in the field of basic life sciences. Professor Kim has achieved outstanding research performances on nerve development, such as identifying the cause of senile retinal degenerative disease and finding retinal nerve cells that distinguish light and darkness in dark conditions. Recently, he discovered intercellular communication, which controls the development of retinal neurons. His findings have contributed to addressing the principles of maintenance and regeneration of retinal neurons. Since joining KAIST, he has presented approximately 20 papers and published in numerous international journals including Cell Reports, Genes and Development, and EMBO Journal. Moreover, he delivered special lectures at international conferences, universities, and institutes around the world.
Professor Dae-Sik Im to Head the Science, Technology and Innovation Office at the Ministry of Science & ICT
(Professor Dae-Sik Im of the Department of Biological Sciences) Professor Dae-Sik Im of the Department of Biological Sciences, a renowned molecular cell biologist, was named to head the Science, Technology and Innovation Office in the Ministry of Science and ICT on August 31. He will be responsible for the oversight of national R&D projects as well as budget deliberation. Joining the KAIST faculty in 2002, he led the Creative Research Center of Cell Division and Differentiation at KAIST. Announcing the nomination of Professor Im, Cheong Wa Dae spokesman Park Soo-Hyun said, “Professor Im will be the best person to lead the innovation of the research infrastructure system for basic research studies. We believe that his expertise and leadership will make a significant impact in enhancing the nation’s science and technology competitiveness. This vice minister position in the Ministry of Science and ICT was newly created in an effort to enhance national science and technology initiatives by President Moon Jae-In. Professor Im said at the news conference, “I would like to make a sustainable, as well as credible, system ensuring the ingenuity of scientists in Korean labs. To this end, I will make every effort to enhance Korea’s innovative research environment in a way to maximize research achievements.”
Professor Won Do Heo Receives 'Scientist of the Month Award'
Professor Won Do Heo of the Department of Biological Sciences was selected as the “Scientist of the Month” for April 2017 by the Ministry of Science, ICT and Future Planning and the National Research Foundation of Korea. Professor Heo was recognized for his suggestion of a new biological research method developing various optogenetics technology which controls cell function by using light. He developed the technology using lasers or LED light, without the need for surgery or drug administration, to identify the cause of diseases related to calcium ions such as Alzheimer’s disease and cancer. The general technique used in optogenetics, that control cells in the body with light, is the simple activation and deactivation of neurons. Professor Heo developed a calcium ion channel activation technique (OptoSTIM1) to activate calcium ions in the body using light. He also succeeded in increasing calcium concentrations with light to enhance the memory capacity of mice two-fold. Using this technology, the desired amount and residing time of calcium ion influx can be controlled by changing light intensity and exposure periods, enabling the function of a single cell or various cells in animal tissue to be controlled remotely. The experimental results showed that calcium ion influx can be activated in cells that are affected by calcium ions, such as normal cells, cancer cells, and human embryonic stem cells. By controlling calcium concentrations with light, it is possible to control biological phenomena, such as cellular growth, neurotransmitter transmission, muscle contraction, and hormone control. Professor Heo said, “Until now, it was standard to use optogenetics to activate neurons using channelrhodopsin. The development of this new optogenetic technique using calcium ion channel activation can be applied to various biological studies, as well as become an essential research technique in neurobiology. The “Scientist of the Month Award” is given every month to one researcher who made significant contributions to the advancement of science and technology with their outstanding research achievement. The awardee will receive prize money of ten million won.
Professor Joonho Choe Appointed as the President of the KSMCB
Professor Joonho Choe of the Biological Sciences Department at KAIST has been elected the 25th president of Korean Society for Molecular and Cellular Biology (KSMCB). His presidency will last one year, beginning on January 1, 2016. Established in 1989, the Society has served as the largest academic gathering in the field of life sciences, holding an international conference every fall. It has more than 12,400 fellows. Professor Choe served as the vice president of KSMC as well as the editor of its journal, Molecules and Cells. He said, “The 2016 International Conference of the KSMCB will take place on October 12-14, 2016 at the COEX Convention and Exhibition Hall in Seoul. This year, we are preparing 20 symposiums and will invite four international renowned keynote speakers in the field including a Nobel Laureate. We hope many people, students and young researchers in particular, from academia and industry will join the conference.” Professor Choe received his doctoral degree from the University of California, Los Angeles (UCLA) after graduating from Seoul National University with his bachelor and master’s degrees.
Professor Sangyong Jon Appointed Fellow of AIMBE
Professor Sangyong Jon of the Department of Biological Sciences at KAIST has been appointed a member of the American Institute for Medical and Biological Engineering (AIMBE) fellowship. Established in 1991, AIMBE is a non-profit organization based in Washington, D.C., representing 50,000 individuals and the top 2% of medical and biological engineers. AIMBE provides policy advice and advocacy for medical and biological engineering for the benefit of humanity. It has had about 1,500 fellows over the past 25 years. Among the members, only 110 are non-American nationalities. Following the appointment of Dr. Hae-Bang Lee, the former senior researcher at the Korean Research Institute of Chemical Technology, and Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering at KAIST, Professor Jon is the third Korean to become an AIMBE fellow. He had an induction ceremony for the appointment of his fellowship at the AIMBE’s Annual Event held on March 15-17, 2015 in Washington, D.C. An authority on nanomedicine, Professor Jon has developed many original technologies including multi-functional Theranostics nano particles for the diagnosis and treatment of diseases. He received the Most Cited Paper Award from Theranostics, an academic journal specialized in nanomedicine, last February. Additionally, Professor Jon is a leading researcher in the field of translational medicine, using a multi-disciplinary, highly collaborative, “Bench to Bedside” approach for disease treatment and prevention. He created a biotechnology venture company and transferred research developments to the industry in Korea.
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